Applicator for cryoanesthesia and analgesia

ABSTRACT

A handheld cryoanesthesia or analgesia device for cooling a target area on cutaneous membranes, mucous membranes, and tissue of the mucocutaneous zone having an elongated body and a thermoelectric cooling system disposed within the elongated body. The thermoelectric cooling system is configured to physically contact and thermally couple the target area of the cutaneous membranes, mucous membranes, and tissue of the mucocutaneous zone to induce cryoanesthesia or analgesia. The thermoelectric cooling system includes a thermally-conductive cold tip, a thermally-conductive cooling power concentrator thermally coupled to the cold tip, at least one Peltier unit module thermally coupled to the cooling power concentrator, a heatsink thermally coupled to at least one Peltier unit module, a power source, at least one thermal sensor, and a controller operably outputting a control signal to the Peltier unit module to maintain a predetermined temperature.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional Application No.62/237,793 filed on Oct. 6, 2015, and U.S. Provisional Application No.62/138,444 filed on Mar. 26, 2015. The entire disclosure of the aboveapplications is incorporated herein by reference

FIELD

The present disclosure relates to a device to deliver rapid anesthesiaor analgesia through cooling of biological tissue, such as cutaneousmembranes, mucous membranes, or tissue of the mucocutaneous zone. Insome exemplary embodiments, the cryoanesthesia device can deliver rapidanesthesia to the surface of the eye, or other biological tissue, at aninjection site to enable more comfortable delivery of medicationdirectly into the eye via intravitreal injection therapy (IVT),retrobulbar injection therapy, subtenon injection therapy,subconjunctival injection therapy, intracameral injection therapy, andthe like.

BACKGROUND AND SUMMARY

This section provides background information related to the presentdisclosure which is not necessarily prior art. This section provides ageneral summary of the disclosure, and is not a comprehensive disclosureof its full scope or all of its features.

Pain is a major limiting factor in many common procedures performed inthe inpatient and ambulatory care settings. A very abbreviated listincludes skin biopsy, fine needle aspiration biopsy, IV insertion,vaccination, injections (including injection of anesthetics), blooddraws, central line placements, and finger and heal pricks for bloodanalysis (glucose measurement). Pharmacologic anesthesia is a primarymethod of pain reduction, but the delivery of local pharmacologicanesthesia usually requires a painful injection. Other methods ofproviding anesthesia include the application of cold temperaturesthrough ice, liquid evaporation, or a low temperature substances. Thesemethods of anesthesia are limited in part by the lack of temperaturecontrol and the inability to tightly focus the tissue area receivinganesthesia. The present device improves patient comfort by providingtightly controlled, focal cooling to the tissue needing anesthesia oranalgesia.

The ocular surface is a tissue surface to which the present device canbe applied, but is not limited to. The ability to deliver medicationdirectly into the eye via intravitreal injection therapy (IVT) hastransformed the treatment landscape of a number of previously blindingdiseases, including macular degeneration and diabetic retinopathy. Thesuccess of these therapies in preventing blindness has resulted in adramatic increase in the number of intravitreal injections performed,with an estimated 4.1 million injections given in the United Statesalone in 2013. The number of indications for IVT continues to expand,increasing utilization of this therapy significantly every year. Theprimary limitations of IVT are patient discomfort, ocular surfacebleeding, and the time constraints of treating the vast number ofpatients requiring this therapy. These drawbacks relate to thedifficulty of delivering ocular anesthesia to the highly vascularizedocular surface.

To give an ocular injection, the physician first provides ocular surfaceanesthesia by one of a number of methods, including the following:topical application of anesthetic drops; a subconjunctival injection oflidocaine; placement of cotton tipped applicators soaked in lidocaineabove the planned injection site, placement of topical anesthetic gel,or some combination of these. Following ocular anesthesia, the physicianor an assistant sterilizes the periocular region by coating it inbetadine or a similar antiseptic. An eyelid speculum is then placed, andthe physician marks the location of the injection using calipers thatguide placement of the needle. The ocular surface is again sterilized,and the physician gives the injection.

Current methods of local anesthesia have unique drawbacks and patientsoften experience discomfort during and after intraocular injections. Thenumber of indications for IVT continues to expand, increasingutilization of this therapy significantly every year. In light of thisneed, we have designed a device to deliver rapid anesthesia andvasoconstriction through the cooling of the surface of the tissue at theinjection site, which will be discussed in greater detail herein.

Most patients receiving IVT receive multiple injections per year. In2004, Friedman and colleagues applied age, ethnicity, and genderspecific rates of AMD to the 2000 US census and estimated that 1.75million Americans had exudate macular degeneration. Population basedestimates suggest that this number will increase to 2.95 million or moreby the year 2020. Using these same principles, Western Europe wasestimated to have over 3.3 million patients with exudative maculardegeneration in 2004. These numbers are likely underestimates of thetrue prevalence of disease. The majority of these patients are receivingIVT multiple times per year in one or both eyes. Recent studies havedemonstrated that IVT is at least as successful as laser therapy totreat vision threatening retinal disease in patients with diabeticretinopathy and retinal vein occlusions, and this has resulted in wideradoption of IVT in these patients. The number of patients with treatableretinal diseases has increased steadily and will continue to grow overthe next several decades. This has led to severe strain on clinic workflow, as IVT is a time-consuming procedure. Vitreoretinal surgeonsperform these injections in busy clinics, frequently treating 60 to 70patients per day. These injections are painful, and ophthalmologiststypically choose one of two anesthesia options for IVT. The most commonis to provide maximal anesthesia by one of two methods, which increasesthe time for patient preparation by several fold. The second option isto provide minimal anesthesia via topical drops, which is more timeefficient, but results in significant patient pain. Both methods requirea technician to prepare each patient. Developing a device to providerapid anesthesia of the ocular surface will improve patient comfort andphysician efficiency.

A recent case report and our own clinical experience show that excellentanesthesia is possible with the application of ice to the ocularsurface. This therapy has been used for patients with allergies tolidocaine, but has much broader implications for all patients receivingIVT. Additionally, histopathologic safety data from historic studies ofcryotherapy for the treatment of retinal tumors have shown that theoperable temperature of the present device will not result in oculartissue damage. Thus, the present device can improve patient comfortwhile simultaneously increasing physician efficiency delivering IVT.

Thermoelectric cooling provides reliable refrigeration as well asprecise temperature control by direct electric feedback, which is hardto achieve with other available cooling techniques such as liquidevaporation, Joule-Thomson cooling, a thermodynamic cycle (e.g., aStirling cooler or vapor compression refrigeration cycle), anendothermic reaction, or a low-temperature substance (e.g., liquidnitrogen). However, current thermoelectric (Peltier) modules have a lowcoefficient of performance (COP) and do not provide sufficient coolingpower flux to maintain tissue at a temperature relevant for anesthesia(e.g., −5° C.) if a single unit is placed with its cooling surface incontact with tissue. As specified in the present teachings, the presentdevice adopts a novel cooling power concentrator that collects thecooling power of multiple (or single) Peltier modules and concentratesthis cooling over a small area, producing a sufficient cooling powerflux required for rapid and sustainable low temperature cooling oftissue. In addition, the cooling power concentrator allows multiplePeltier modules to be distributed over a large area, minimizing the heatflux rejected from Peltier modules to the heat sink and hence relaxingthe heat dissipation requirements of the heat sink.

According to the principles of the present teachings, a cryoanesthesiaor analgesia device and method of use in ocular treatments is providedthat allows for rapid administration of anesthesia to the eye, forexample, for administration of intravitreal injections, for example. Insome embodiments, by providing cooling of the conjunctiva and sclera atthe injection site, patient discomfort is minimized.

In some embodiments, the cryoanesthesia device of the present teachingsis designed to achieve a cold temperature quickly by means of athermoelectric (Peltier) device, liquid evaporation, Joule-Thomsoncooling, a thermodynamic cycle (e.g., a Stirling cooler or vaporcompression refrigeration cycle), an endothermic reaction, and alow-temperature substance (e.g., liquid nitrogen). The cryoanesthesiadevice may be sufficiently sized to be handheld or be part of a largerunit, and may include safety mechanisms to limit cooling to a definedtemperature, maximum heat flux, or time period in order to preventdamage to ocular or other biological tissue. In some embodiments, thecryoanesthesia device of the present teachings can comprise anapplicator attached to a larger cooling unit. The cryoanesthesia devicemay be a stand-alone, hand-held unit. Use of the cryoanesthesia deviceof the present teachings improves anesthesia and reduces pre-injectionprep time for patients and physicians.

It should be understood, however, that the cryoanesthesia device of thepresent teachings can be used to decrease pain in any part of the body,including, but not limited to, the cutaneous membranes, mucousmembranes, and tissue of the mucocutaneous zone.

Further areas of applicability will become apparent from the descriptionprovided herein. The description and specific examples in this summaryare intended for purposes of illustration only and are not intended tolimit the scope of the present disclosure.

DRAWINGS

The drawings described herein are for illustrative purposes only ofselected embodiments and not all possible implementations, and are notintended to limit the scope of the present disclosure.

FIG. 1 is a perspective view illustrating a cryoanesthesia device inaccordance with the principles of the present teachings;

FIG. 2 is a partial cross-sectional view illustrating the thermoelectriccooling system in accordance with some embodiments of the presentteachings;

FIG. 3 is an enlarged perspective view of a cold tip of thecryoanesthesia device in accordance with some embodiments of the presentteachings;

FIG. 4 is an enlarged perspective view of an air circulation system inaccordance with some embodiments of the present teachings;

FIGS. 5A-5B are graphs illustrating simultaneously measured tiptemperature, and power and voltage versus time; and

FIGS. 6A-6E is a series of perspective views of cryoanesthesia deviceshaving an IVT needle, with portions removed for clarity, in accordancewith some embodiments of the present teachings.

Corresponding reference numerals indicate corresponding parts throughoutthe several views of the drawings.

DETAILED DESCRIPTION

Example embodiments will now be described more fully with reference tothe accompanying drawings.

Example embodiments are provided so that this disclosure will bethorough, and will fully convey the scope to those who are skilled inthe art. Numerous specific details are set forth such as examples ofspecific components, devices, and methods, to provide a thoroughunderstanding of embodiments of the present disclosure. It will beapparent to those skilled in the art that specific details need not beemployed, that example embodiments may be embodied in many differentforms and that neither should be construed to limit the scope of thedisclosure. In some example embodiments, well-known processes,well-known device structures, and well-known technologies are notdescribed in detail.

The terminology used herein is for the purpose of describing particularexample embodiments only and is not intended to be limiting. As usedherein, the singular forms “a,” “an,” and “the” may be intended toinclude the plural forms as well, unless the context clearly indicatesotherwise. The terms “comprises,” “comprising,” “including,” and“having,” are inclusive and therefore specify the presence of statedfeatures, integers, steps, operations, elements, and/or components, butdo not preclude the presence or addition of one or more other features,integers, steps, operations, elements, components, and/or groupsthereof. The method steps, processes, and operations described hereinare not to be construed as necessarily requiring their performance inthe particular order discussed or illustrated, unless specificallyidentified as an order of performance. It is also to be understood thatadditional or alternative steps may be employed.

When an element or layer is referred to as being “on,” “engaged to,”“connected to,” or “coupled to” another element or layer, it may bedirectly on, engaged, connected or coupled to the other element orlayer, or intervening elements or layers may be present. In contrast,when an element is referred to as being “directly on,” “directly engagedto,” “directly connected to,” or “directly coupled to” another elementor layer, there may be no intervening elements or layers present. Otherwords used to describe the relationship between elements should beinterpreted in a like fashion (e.g., “between” versus “directlybetween,” “adjacent” versus “directly adjacent,” etc.). As used herein,the term “and/or” includes any and all combinations of one or more ofthe associated listed items.

Although the terms first, second, third, etc. may be used herein todescribe various elements, components, regions, layers and/or sections,these elements, components, regions, layers and/or sections should notbe limited by these terms. These terms may be only used to distinguishone element, component, region, layer or section from another region,layer or section. Terms such as “first,” “second,” and other numericalterms when used herein do not imply a sequence or order unless clearlyindicated by the context. Thus, a first element, component, region,layer or section discussed below could be termed a second element,component, region, layer or section without departing from the teachingsof the example embodiments.

Spatially relative terms, such as “inner,” “outer,” “beneath,” “below,”“lower,” “above,” “upper,” and the like, may be used herein for ease ofdescription to describe one element or feature's relationship to anotherelement(s) or feature(s) as illustrated in the figures. Spatiallyrelative terms may be intended to encompass different orientations ofthe cryoanesthesia device in use or operation in addition to theorientation depicted in the figures. For example, if the cryoanesthesiadevice in the figures is turned over, elements described as “below” or“beneath” other elements or features would then be oriented “above” theother elements or features. Thus, the example term “below” can encompassboth an orientation of above and below. The cryoanesthesia device may beotherwise oriented (rotated 90 degrees or at other orientations) and thespatially relative descriptors used herein interpreted accordingly.

It should be understood that the present teachings will be described inconnection with an eye. However, the principles of the present teachingsare equally applicable for use with other biological tissue, includingskin, organs, membranes, nasal mucosa, and the like. Accordingly, thedisclosure should not be regarded as being limited to eyes, unlessotherwise limited in the claims, but may include all biological tissue.

According to the principles of the present invention, a cryoanesthesiadevice is provided having advantageous construction and method of use.In some embodiments, the cryoanesthesia device is configured to providerapid anesthesia to the ocular surface to aid in the administration ofintravitreal injections or other medical procedures. Generally, theocular surface is regarded as that portion of an eye that is exposed tothe external environment. However, in some embodiments, the ocularsurface can include the cornea and its major support tissue, theconjunctiva. In a wider anatomical, embryological, and also functionalsense, the ocular mucosal adnexa (i.e. the lacrimal gland and thelacrimal drainage system) can be part of the ocular surface. Thecryoanesthesia device of the present teachings rapidly achieves coldtemperatures, such as through thermoelectric cooling, utilizing athermodynamic cycle, utilizing an endothermic reaction, or the use of acold substance such as liquid nitrogen to impart localized cooling toproduce regional anesthesia. Such cryoanesthesia slows conduction ofpain fibers in the conjunctiva (outermost layer of the eye) and thesclera (white of the eye).

The present teachings may have application in rapid, complete ocularanesthesia that can be given immediately prior to intravitrealinjections, fine-needle aspiration biopsies, lacrimal and nasolacrimalsystem biopsies, and a wide variety of peri-ocular procedures including,but limited to, eyelid biopsies, peri-orbital injections ofpharmacologic anesthetics, and eyelid lesion excisions. Accordingly, thepresent teachings provide numerous advantages, including but not limitedto decreased time to achieve ocular anesthesia compared to currentmethods, more complete ocular anesthesia resulting in decreased painfrom intravitreal injections, decreased ocular surface bleeding, andavoidance of the side effects of topical and injectable anestheticmedications.

The present teachings have application in rapid anesthesia of cutaneousmembranes, mucous membranes, and tissue of the mucocutaneous zone. Thecooling of nerve conduction can facilitate decreased pain prior toinjections, IV placement, incisional and excisional biopsies,fine-needle aspiration biopsies, and a variety of other proceduresincluding but not limited to finger sticks prior to glucose measurement.

With reference to the figures, a device 10 is provided having anadvantageous construction and method of use for cryoanesthesia and/oranalgesia (however, for brevity, device 10 will be referred to ascryoanesthesia device 10, but will have utility in both cryoanesthesiaand analgesia applications). Specifically, in some embodiments asillustrated in FIGS. 1-4, cryoanesthesia device 10 can comprise anelongated body 12 having a proximal end 14 and a distal end 16. As willbe appreciated from the foregoing description, cryoanesthesia device 10can be sized and shaped to be a handheld portable device conducive touse in a wide variety of medical procedures in both in-patient andout-patient facilities. Elongated body 12 can be shaped to include agripping portion 22 generally disposed at a balanced midpoint locationand/or a location generally adjacent proximal end 14 or distal end 16.In the illustrated embodiment, gripping portion 22 is disposed generallybetween a midpoint location and distal end 16.

With continued reference to FIGS. 1-4, in some embodiments, elongatedbody 12 can comprise a neck portion 20 providing a transition between aproximal portion 18 and gripping portion 22. In some embodiments,gripping portion 22 can define a different cross-sectional shaperelative to proximal portion 18 (e.g. a narrower shape), therebyresulting in neck portion 20 providing a transitional profile therebetween. It should be understood, however, that in some embodimentsgripping portion 22 and/or proximal portion 18 can serve as a grippingportion to facilitate manipulation by a user. Therefore, the chosennomenclature for proximal portion 18 and gripping portion 22 should notbe regarded as limiting the invention, unless otherwise claimed. In someembodiments, cryoanesthesia device 10 is a handheld instrument measuringapproximately 6 to 10 inches in length and 1 to 1.5 inches in diameter.However, alternative sizes are envisioned.

Generally, in some embodiments, cryoanesthesia device 10 cools a targetarea on the ocular surface to a predetermined temperature (e.g. in therange of about 5° C. to about −10° C.) within a predetermined amount oftime (e.g. in the range of about 1 second to about 60 seconds, in therange of about 1 second to about 120 seconds, or longer), therebyinducing cryoanesthesia required for ocular procedures, such asintravitreal drug injection. It should be understood that othertemperatures ranges are included in the present teachings, includingpredetermined temperatures in the range of about 5° C. to about −50° C.and in the range of about 5° C. to about −90° C. In some embodiments,cryoanesthesia device 10 comprises a thermoelectric (Peltier) coolingsystem 24 disposed within at least a portion of elongated body 12 forproviding low temperature cooling of a cooling tip 26 disposed on distalend 16 of elongated body 12 to induce cryoanesthesia in the ocularsurface. It should be understood that in some embodiments, a coolingsystem can comprise one or a combination of thermoelectric (Peltier)devices, liquid evaporation, Joule-Thomson cooling, a thermodynamiccycle (e.g., a Stirling cooler or vapor compression refrigerationcycle), an endothermic reaction, or a low-temperature substance (e.g.,liquid nitrogen), which may or may not undergo a phase change.

In some embodiments, thermoelectric cooling system 24 comprises a coldtip 26, a power source 28, a controller 30, a cooling power concentrator32, one or more Peltier unit modules 34, and a heat sink 36. It shouldbe understood that, in some embodiments, thermoelectric cooling system24 may include a heating element (not shown) that operates inconjunction with the cooling elements to precisely maintain a desiredtemperature and/or heat flux.

With particular reference to FIG. 3, in some embodiments, cold tip 26can be made of a thermally conductive material, such as a metal, and canbe sized to be generally equal to or smaller than the target area of theocular or other biologic surface. In some embodiments, the target areaon the eye is a region that begins at the corneal limbus and extendsanywhere from 2 mm to over 8 mm posterior to the limbus. In someembodiments, the end of the cold tip 26 is circular, approximately 6 mmin diameter including thermally insulating outer ring member 64, whichwould correspond to the target area to be cooled. The thermallyinsulating outer ring member 64 restricts the area being cooled withinthe target area, which is touched by the thermally conductive cold tip26, preventing damage to adjacent cells outside the target area. In someembodiments, the thermally insulating outer ring member 64 visuallyguides the target area but does not touch the ocular or other biologicsurface to prevent heat exchange with the thermally insulating outerring member 64. In some embodiments, a larger (or smaller) size of thecold tip can be used to provide anesthesia to cutaneous membranes,mucous membranes, or tissue of the mucocutaneous zone. In theillustrated embodiment, cold tip 26 is cylindrical in shape; however, itshould be understood that alternative shapes are envisioned, includingpolygonal, oval, crescent, or any other conducive shape.

In some embodiments, power source 28 comprises a portable power source,such as a battery, capacitor, or similar device. In some embodiments,power source 28 can comprise a rechargeable lithium ion battery pack (28Wh), which provides sufficient energy on a single charge to operatecryoanesthesia device 10 at −10° C. for approximately one hour. However,in some embodiments, power source 28 can comprise a non-portable powersource.

Controller 30 can comprise a temperature regulating feedback loop tomaintain highly accurate temperature control and/or a timed lockoutmechanism to prevent excessive cooling. More particularly, in someembodiments, controller 30 can comprise a temperature sensor 38 operablycoupled with at least one member of a thermal circuit comprising coldtip 26, cooling power concentrator 32, Peltier unit modules 34, heatsink 36, surrounding environment, and the ocular surface of the patientto output a temperature signal in response to a detected temperature. Inthis way, controller 30 receives the temperature signal and is operableto control an operating temperature of Peltier unit modules 34 viacontrolled current flow, controlled voltage, and/or pulse widthmodulation (PWM) of the DC battery source, thereby precisely regulatingan operating temperature of cryoanesthesia device 10. In someembodiments, temperature sensor 38 is arranged to directly measure thetemperature of the ocular surface of the eye or any portion of thethermal circuit using any one or a number of thermal sensors, such asbut not limited to thermistors, thermocouples, and resistance or opticalthermometers. Controller 30 can then compute temperature and/or heatflux. Controller 30 can maintain a predetermined temperature ortemperature range using a constant value, a pulse of certain magnitudeand duration, or a more complex prescribed pattern. In some embodiments,cryoanesthesia device 10 can automatically power off if the tiptemperature falls below a certain temperature (e.g., −12° C.) to ensurea safe operating temperature range, and/or if a battery temperatureexceeds 60° C. or the heat sink temperature exceeds 50° C. In someembodiments, controller 30 can operate on the basis of applied,measured, or desired heat fluxes rather than applied, measured, ordesired temperatures.

As described, controller 30 may further comprise a timed lockoutmechanism that monitors and controls, via an integrated timer, theduration of cooling. In this way, controller 30 is capable of monitoringand achieving sufficient cooling of the target area on the ocularsurface and prohibit excessive cooling thereof. In some embodiments,this timed cooling lockout is set to a predetermined time ofapproximately 3 seconds to approximately 60 seconds; however, additionaldurations are anticipated by the present teachings. It should beunderstood that the timed lockout mechanism may be used in combinationwith the temperature regulating feedback loop to both actively monitorand control both a measured temperature and a measured time.

In some embodiments, cooling power concentrator 32 is a generally, butnot limited to, elongated concentrator made of a thermally-conductivematerial, such as but not limited to metal. Cooling power concentrator32 can be disposed along a central longitudinal axis of elongated body12, and collects cooling powers of multiple Peltier units or that of asingle Peltier unit. In some embodiments, cooling power concentrator 32can be polyhedron in shape, and the cooling power collected from thesurface(s) in contact with Peltier unit(s) is concentrated to one ormore surfaces whose aggregate area is less than that of the Peltier unitcooling surface(s) at which collection occurs. However, it should beunderstood that cooling power concentrator 32 can have other shapes,including cylinder, cone, conical cylinder, sphere, hemisphere, or anyother shapes that provide collecting and concentrating of cooling power.In such embodiments, Peltier unit modules 34 can be shaped to define acomplementary surface to enhance surface area contact between Peltierunit modules 34 and cooling power concentrator 32 to facilitatethermoelectric cooling.

In some embodiments, cooling power concentrator 32 can be shaped toterminate at a compressible tip 42 that can be used to replace cold tip26 prior to use and maintain its sterility. Compressible tip 42 cancomprise a plurality of tapered flange members 44 extending radiallyfrom a main body portion 46 of cooling power concentrator 32. Theplurality of tapered flange members 44 collectively form a central boresized to receive cold tip 26 therein to provide a mechanical and thermalcoupling there between. The plurality of tapered flange members 44 aresized and shaped to provide independent flexibility to provide themechanical coupling of cold tip 26 in response to compression exertedvia a compression ring 48 threadedly engaging corresponding threadsdisposed on an exterior surface of the plurality of tapered flangemembers 44. In this way, threaded engagement of compression ring 48about the plurality of tapered flange members 44 results in theplurality of tapered flange members 44 being urged into a tighter,narrower nested relationship thereby exerting a compressive, retainingforce upon cold tip 26. Accordingly, threaded manipulation ofcompression ring 48 about the plurality of tapered flange members 44 canprovide selective coupling and decoupling of cold tip 26 with coolingpower concentrator 32. It should be understood, however, that otherfixture mechanisms such as a mechanical latch, magnetic coupling, bolt,or adhesive can be used to fix the cold tip. This is conductive topermitting cold tip 26 to be selectively replaced due to sterilityand/or operational concerns. It should be understood that cold tip 26 isthus a replaceable tip that defines the contact cooling region ofcryoanesthesia device 10 and provides a sterile surface for tissuecontact. A replaceable or sterilizable tip coating 70 may also beintegrated with cold tip 26 to provide a sterile surface for tissuecontact.

In some embodiments, one or more Peltier unit modules 34 are disposedalong, such as in an array, at least a portion of cooling powerconcentrator 32 to provide thermoelectric cooling of cooling powerconcentrator 32 and, thus, cold tip 26. It should be understood thatPeltier unit module 34 can be configured as a single cooling element ora plurality of cooling elements. However, it should be understood thatthere are particular benefits to employing a plurality of Peltier unitmodules 34, such as but not limited to redundancy of operation and thepotential to source readily-available units from established industry.In some embodiments, the hot surface of Peltier unit module 34 isconfigured to be vertical with respect to central cooling portion 62 ofcold tip 26. However, it should be understood that the hot surface ofPeltier unit module 34 can be parallel or in any angle with respect tocentral cooling portion 62 of cold tip 26 depending on the desireddirection of heat rejection from Peltier unit modules 34. In someembodiments, the plurality of Peltier unit modules 34 are operablycoupled to power source 28 and controller 30 in such a way as to permitelectrically parallel operation, thereby permitting cryoanesthesiadevice 10 to continue operation despite failure of one or more Peltierunit modules 34. In such a case, controller 30, and its associatedfeedback loop control system, can increase cooling output of theoperable Peltier unit modules 34 to achieve desired cooling and/orduration performance.

While thermoelectric cooling has the advantages of being lightweight,small, solid-state (thus no fluids or moving parts), and electricallydriven (thus allowing straightforward control of temperature), itrejects a large amount of heat that must be carefully managed.Cryoanesthesia device 10 provides a unique design for efficient heatspreading and dissipation. As described herein, cooling powerconcentrator 32 is thermally conductive and is cooled by one or morePeltier unit modules 34 to quickly and reliably maintain a predeterminedtemperature of cold tip 26. The Peltier unit modules 34 are distributedto efficiently spread the heat rejected from Peltier unit modules 34 toheat sink 36 and therefore promote efficient cooling, which reduces thesize of heat sink 36 and may enhance visual clearance between cold tip26 and a user's eye. Heat sink 36 is made of a thermally conductivematerial to efficiently spread the heat rejected from Peltier unitmodules 34. In some embodiments, heat sink 36 is radially disposed aboutcooling power concentrator 32 and Peltier unit modules 34. In otherwords, heat sink 36 radiates outwardly from a central longitudinal axisof cryoanesthesia device 10. However, it should be understood that heatsink 36 can radiate heat in other directions depending on the relativeangle of the hot surface of Peltier unit module 34 with respect tocentral cooling portion 62 of cold tip 26. In some embodiments, heatsink 36 is disposed generally within gripping portion 22 and/or neckportion 20 of elongated body 12, thereby providing localized heatsinking directly near Peltier unit modules 34 and cold tip 26, whilemaintaining a narrow shape of gripping portion 22 for improved visualclearance during use and handheld capability.

To facilitate heat dissipation from heat sink 36, an air circulationsystem 50 is provided for circulating air across fins or other featuresof heat sink 36. In some embodiments, a fan 52 (see FIG. 1) powered bypower source 28 is actuated to draw air in from one or more inletopenings 54. In some embodiments, inlet openings 54 comprise a pluralityof fin channels 56 formed in heat sink 36 that are used to increase thesurface area of heat sink 36 to facilitate heat transfer. In someembodiments, the surface roughness of heat sink 36 can be large tofurther increase the surface area of heat sink 36 in contact with air.Air passes along the plurality of fin channels 46 formed in heat sink 36and generally surrounded by gripping portion 22 of elongated body 12,along a direction generally, but not limited to, parallel to the centrallongitudinal axis of cryoanesthesia device 10, and exits from one ormore outlet openings 58 at a location far from cold tip 26. It should beunderstood that the direction of air circulation can be perpendicular orin another angle to the central longitudinal axis of cryoanesthesiadevice 10 depending on the relative angle of the hot surface of Peltierunit modules 34 with respect to the surface of cold tip 26. Locatingoutlet openings 58 far from cold tip 26 not only reduces convection lossat the tip surface of cold tip 26, but also minimizes dryness of thepatient's tissues due to airflow. Alternatively, air may be forced inthe opposite direction and exit near the cold tip.

In some embodiments, cold tip 26 comprises a central cooling portion 62being thermally coupled to cooling power concentrator 32, and athermally-insulating ring member 64 surrounding a peripheral side ofcentral cooling portion 62. Thermally-insulating ring member 64 isdisposed to permit central cooling portion 62 to maintain an exposedcontact tip configured to physically contact and thermally couple to atarget area of the ocular surface, while simultaneously providing visualguidance regarding the position of the area to be cooled that is touchedby the central cooling portion 62 with respect to the positions ofnearby objects such as corneal stem cells and thereby prevent excessivecooling of these objects. In some embodiments, thermally-insulating ringmember 64 includes an active heating element that controls thetemperature adjacent to the cooled region in order to limit damage tosurrounding tissue caused by cooling spread. In some embodiments,central cooling portion 62 of cold tip 26 defines an area ofapproximately 10 mm² to approximately 900 mm² (e.g. 3 mm×3 mm to 10×10mm²).

With continued reference to FIG. 3, in some embodiments, central coolingportion 62 of cold tip 26 can comprise targeting indicia 66 formedthereon configured to contact the target area of the ocular surface andprovide a temporary marking for locating an anesthetized region. Forexample, in some embodiments, targeting indicia 66 can comprise a pairof protruding or indented features formed on cold tip 26 thattemporarily results in markings on the ocular surface following removalof cryoanesthesia device 10. These markings can be then used to properlylocate an anesthetized region for placement of the IVT needle (e.g.,placement of the intravitreal injection needle 3 mm or 4 mm from thecorneal limbus). It should be understood that different targetingindicia 66 are envisioned, including but not limited to a circular orring-shaped protrusion, multiple protrusions, or any other shapes thatprovide temporary markings.

In some embodiments, cryoanesthesia device 10 can comprise areplaceable/disposable tip coating 70 to provide a sterile surface forocular contact and to mitigate formation of an ice adhesion betweencryoanesthesia device 10 and the patient's eye. In some embodiments, tipcoating 70 can comprise a hydrophobic polymer layer to mitigate iceadhesion between the cryoanesthesia device and tissue.

In some embodiments, a first switch member 80 is provided for actuationof cryoanesthesia device 10. In some embodiments, switch member 90 canbe used to set the cold tip temperature and timer duration, as well aspower the Peltier modules. In some embodiments, operation of firstswitch member 80 comprises: 1) clockwise rotation to increase the coldtip set temperature, 2) counter-clockwise rotation to decrease the coldtip set temperature, 3) clockwise rotation while the first switch member80 is pushed, to increase the timer duration, 4) counter-clockwiserotation while the first switch member 80 is pushed, to decrease thetimer duration, and 5) double-pressing to activate the Peltier modules.

A second switch member 82 located near gripping portion 22 can be usedto activate (or deactivate) the timer. When the timer is activated,cryoanesthesia device 10 can produce audible indicia, such as twoconsecutive beeping sounds at low and high frequencies followed bybeeping sounds every 10 seconds during the timer duration, and finallytwo long consecutive beeping sounds at high and low frequencies when thetimer duration has expired. In some embodiments, first switch member 80can be pushed before the set time is reached to terminate the timerfunction. It should be understood that cryoanesthesia device 10 cancomprise any one of a number of control inputs, indicia, and techniques;accordingly, the presently described inputs, indicia, and techniquesshould not be regarded as limiting the invention.

During use, in some embodiments, cryoanesthesia device 10 is positionedin contact with the patient's eye such that cold tip 26 (or tip coating)is in physical direct contact with the target area of the ocularsurface. Cryoanesthesia device 10 can be actuated “ON” via switch 80either before or after being placed in contact with the patient's eye.Actuation of cryoanesthesia device 10 thereby initiates rapid cooling ofcold tip 26 by controller 30, cooling power concentrator 32, Peltierunit modules 34, heat sink 36, and air circulation system 50, whilesimultaneously marking the eye and anesthetizing the target area of theocular surface. Following anesthetizing of the target area, a physicianor care provider can then perform additional procedures, such asadministering IVT. In some embodiments, a user may set a desired coldtip temperature and timer duration and then double-press first switchmember 80 to activate Peltier modules 34 to bring cold tip 26 to a settemperature point (e.g. −10° C.). Cold tip 26 can then be brought intocontact with the patient's eye and the timer actuated. Cryoanesthesiadevice 10 then maintains the set temperature point for a setpredetermined duration (e.g. 10 seconds) and then produces indicia suchas, but not limited to, beep sounds or vibration. After the timerduration, cryoanesthesia device 10 can automatically adjust the tiptemperature to a higher temperature (e.g., −2° C.) to minimize iceadhesion between tissues and cold tip 26, and then return to ambienttemperature. As illustrated in FIGS. 5A and 5B, tip temperature, alongwith power and voltage data, are illustrated along a time axis duringoperation.

In some embodiments, as illustrated in FIGS. 6A-6E, the cryoanesthesiadevice performs both anesthesia and injection (e.g., intravitrealinjection). In some embodiments, a cooling power concentrator 91 issterilized and replaceable. In some embodiments, cooling powerconcentrator 91 first induces cryoanesthesia at a tip 92, after whichthe cryoanesthesia device performs injection (e.g., intravitrealinjection). In some embodiments, a drug container 93 is placed insidethe cooling power concentrator 91, as illustrated in FIG. 6B. In someembodiments, a solenoid 96 or similar feature pushes the drug container93, compresses a spring 95 or similar feature, and inserts needle 94within tissue (e.g., eye tissue). In some embodiments, solenoid 96 orsimilar feature controls the depth of needle insertion within tissue. Insome embodiments, solenoid 96 or similar feature squeezes drug container93, causing drug to be injected, as illustrated in FIG. 6D. In someembodiments, needle 94 is placed outside of cooling power concentrator97, as illustrated in FIG. 6E. It should be understood, however, thatthe description above is provided for the purposes of illustration anddoes not limit the present teachings.

The foregoing description of the embodiments has been provided forpurposes of illustration and description. It is not intended to beexhaustive or to limit the disclosure. Individual elements or featuresof a particular embodiment are generally not limited to that particularembodiment, but, where applicable, are interchangeable and can be usedin a selected embodiment, even if not specifically shown or described.The same may also be varied in many ways. Such variations are not to beregarded as a departure from the disclosure, and all such modificationsare intended to be included within the scope of the disclosure.

What is claimed is:
 1. A device for cooling a target area of cutaneousmembrane, a mucous membrane, or tissue of a mucocutaneous zone, thedevice comprising: an elongated body having a griping portion tofacilitate handheld manipulation by a user, the elongated body having aproximal end and a distal end; a thermoelectric cooling system disposedwithin at least a portion of the elongated body, the thermoelectriccooling system configured to physically contact and thermally couple thetarget area to include cryoanesthesia or analgesia, the thermoelectriccooling system having: a thermally-conductive cold tip adapted tothermally contact the target area, the cold tip being disposed on thedistal end of the elongated body; a thermally-conductive cooling powerconcentrator thermally coupled to the cold tip; at least one Peltierunit module thermally coupled to the cooling power concentrator, thePeltier unit module operable to induce cooling of the powerconcentrator; a power source; a thermal sensor detecting a temperatureor heat flux of at least one of the cold tip, the cooling powerconcentrator, the Peltier unit module, a surrounding environment, andthe target area, the thermal sensor outputting a temperature or heatflux signal; a controller operably outputting a control signal to thePeltier unit module in response to the temperature or heat flux signaland a predetermined temperature or heat flux; and a heat sink thermallycoupled to the Peltier unit module and disposed inside the elongatedbody.
 2. The device according to claim 1 wherein the at least onePeltier unit module comprises a plurality of Peltier unit modules. 3.The device according to claim 2 wherein the plurality of Peltier unitmodules are electrically coupled in a parallel array.
 4. The deviceaccording to claim 2 wherein the plurality of Peltier unit modules areelectrically coupled in a series array.
 5. The device according to claim2 wherein the plurality of Peltier unit modules are electrically coupledin parallel.
 6. The device according to claim 1 wherein the coolingpower concentrator is an elongated concentrator being generallyrectangular in cross-section, the at least one Peltier unit module beingdisposed on a side of the elongated concentrator.
 7. The deviceaccording to claim 1 wherein the cooling power concentrator extendsalong a longitudinal axis of the elongated body.
 8. The device accordingto claim 1 wherein the cold tip comprises targeting indicia formedthereon configured to produce a temporary indication on the target area.9. The device according to claim 8 wherein the targeting indiciacomprises a pair of protrusions for producing temporary indentations onthe target area.
 10. The device according to claim 1, furthercomprising: an air circulation system having a fan member urging passageof air across the heat sink to facilitate heat transfer, the fan memberbeing disposed within the elongated body.
 11. The device according toclaim 10 wherein the air circulation system comprises: an air inletdisposed adjacent to the cold tip on the distal end of the elongatedbody; a plurality of fin channels extending from the heat sink; and anair outlet extending through the elongated body at a location toward theproximal end of the elongated body relative to the air inlet.
 12. Thedevice according to claim 10 wherein the air circulation systemcomprises: an air outlet disposed adjacent to the cold tip on the distalend of the elongated body; a plurality of fin channels extending fromthe heat sink; and an air inlet extending through the elongated body ata location toward the proximal end of the elongated body relative to theair outlet.
 13. The device according to claim 11 wherein the pluralityof fin channels are generally surrounded by the gripping portion of theelongated body and the flow of air along the plurality of fin channelsis generally parallel to a longitudinal axis of the elongated body. 14.The device according to claim 11 wherein the plurality of fin channelsare radially extending from the heat sink.
 15. The device according toclaim 1 wherein the cooling power concentrator comprises a compressibleend, the compressible end having a plurality of flange members extendingthereof, the plurality of flange members being sized to mechanically,thermally, and releasably couple the cold tip to the cooling powerconcentrator.
 16. The device according to claim 15 wherein thecompressible tip comprises a compression ring threadedly engaging theplurality of flange members and urging the plurality of flange membersinto engagement with the cold tip.
 17. The device according to claim 1,further comprising: a coating disposed about the cold tip, the coatingcovering the cold tip to prevent direct physical contact between thecold tip and the target area and permit the thermal coupling between thecold tip and the target area.
 18. The device according to claim 17wherein a surface of the cover is hydrophobic.
 19. The device accordingto claim 1, further comprising: a thermal insulating ring generallysurrounding a peripheral side of the cold tip to reduce thermal exposureof adjacent cells outside of the target area.
 20. The device accordingto claim 19 wherein the thermal insulating ring comprises an activeheating element.
 21. The device according to claim 1 wherein the powersource is a portable power source.
 22. The device according to claim 1wherein the gripping portion of the elongated body is narrower than aproximal portion of the elongated body, the proximal portion beingadjacent the proximal end.
 23. The device according to claim 1 whereinthe device includes an injecting mechanism comprising: a disposableneedle; a syringe; a syringe plunger to advance the needle into thetarget area and inject fluid from the syringe into the target area; aretracting element to withdraw the needle back into the device followingcompletion of the injection.
 24. The device according to claim 1 whereinthe device contains a switch that activates an injection.
 25. The deviceaccording to claim 1 wherein the cold device tip is sterile.
 26. Thedevice according to claim 1 wherein the device cold tip has a curvedphalange to retain tissue.
 27. The device according to claim 1, whereinthe thermal sensor detects a temperature or heat flux of at least one ofthe cooling power concentrator, the Peltier unit module, a surroundingenvironment, cold tip, the thermal sensor outputting a temperature orheat flux signal.
 28. The device according to claim 27, wherein thethermal sensor detects the temperature or heat flux of the cold tip. 29.The device according to claim 1, wherein the heat sink is radiallydisposed about the cooling power concentrator.
 30. The device accordingto claim 29, wherein the heat sink in a gripping portion, a neck portionor both a gripping and a neck portion of the device.
 31. A method ofapplying cryoanesthesia or analgesia to a target area of cutaneousmembrane, a mucous membrane, or tissue of a mucocutaneous zone, themethod comprising: providing a device having: an elongated body having agripping portion to facilitate handheld manipulation by a user, theelongated body having a proximal end and a distal end; a thermoelectriccooling system disposed within at least a portion of the elongated body,the thermoelectric cooling system configured to physically contact andthermally couple the target area to induce cryoanesthesia or analgesia,the thermoelectric cooling system having: a thermally-conductive coldtip adapted to thermally contact the target area, the cold tip beingdisposed on the distal end of the elongated boy; a thermally-conductivecooling power concentrator thermally coupled to the cold tip; at leastone Peltier unit module thermally coupled to the cooling powerconcentrator, the Peltier unit module operable to induce cooling of thecooling power concentrator; a power source; a thermal sensor detecting atemperature of at least one of the cold tip, the cooling powerconcentrator, the Peltier unit module, and the target area, the thermalsensor outputting a temperature signal; a controller operably outputtinga control signal to the Peltier unit module in response to thetemperature signal and a predetermined set temperature; and a heat sinkthermally coupled to the Peltier unit module and disposed inside theelongated body, actuating the controller to achieve cooling of the coldtip to a temperature prior to or simultaneously with placement of thecold tip upon the target area; and achieving sufficient cooling of thetarget area to cryoanesthetize or analogize the target area.